tbuckley/cabot-search huggingface dataset:
Abstract 15391: Transcriptomic Expression Changes in Embryonic Mouse Hearts Following Single-Dose Maternal Binge Alcohol Consumption: Implications for Congenital Heart Defects
Authors: Anagha Srivatsa, Darya Sulkouskaya, Richard Shao, Jose D Alvarez, Shreya Chordiya, Jesu R Valencia, Brandon Le, Shibu Yooseph, Pal Pacher, Steven N Ebert
Journal: Circulation (2022)

Introduction: Prenatal alcohol exposure is a risk factor for congenital heart defects, but it is unclear how alcohol exposure in utero leads to disruption of normal cardiovascular development. To gain insight into the transcriptomic pathways involved, we performed RNA-sequencing (RNA-seq) of embryonic mouse hearts 24h (E10.5) and 48h (E11.5) after a single dose of maternal alcohol. Hypothesis: Maternal binge alcohol consumption at E9.5 disrupts expression of specific embryonic genes important for heart development. Methods: Alcohol treatment (2.5g/Kg ethanol in saline) or control solution (0.9% saline) was administered to pregnant C57Bl/6 mice via single oral gavage at E9.5. Embryonic hearts were collected 24h and 48h later for RNA isolation and analysis by RNA-Seq and quantitative PCR (qPCR) methods. Reactome® pathway analysis was performed to determine which were most affected. Results: Of the nearly 20,000 genes expressed in the embryonic heart, we found remarkably few (less than 0.1%) showing significant alterations in expression. Most of the gene expression changes induced by alcohol occurred within 24h and were largely genes involved in transcriptional regulation or signaling pathways. In particular, Wnt7a showed significant ( p=0.013 ) and substantial change (nearly 5-fold decrease relative to control expression, n=11 per group) in response to maternal binge alcohol 24h post-gavage. Similar results were observed for Wnt7a at 48h post-binge (p=0.043, n=8/group). Further analyses showed that Wnt -related genes, Dkk2, Rtl1,Wnt3, Wnt6, and Wnt10a showed significantly decreased expression and Wnt11 showed significantly increased expression in the embryonic heart 24h post-binge alcohol. Conclusions: These results suggest that Wnt7a and related signaling pathway genes are disrupted by alcohol action in the embryonic heart, thereby opening new avenues for investigation into molecular underpinnings of alcohol-induced congenital heart defects.
Abstract 15365: The Regulatory Role of Sirtuin 6 in Diabetic Cardiomyopathy
Authors: Yang Wang, Molly Enrick, James Gadd, Cody Juguilon, Alyssa Clark, Chris Kolz, William M Chilian, Yanqiao Zhang, Liya Yin
Journal: Circulation (2022)

Introduction: DCM is a complex disease with many possible causes and multifactorial pathophysiology, but its underlying mechanisms are poorly understood, and no specific therapeutic guideline has yet been established. Increasing evidence suggests that coronary microvascular dysfunction (CMD) might be one of the primary mechanisms in DCM development. CMD is characterized by impaired endothelial-dependent vasodilation, but detailed mechanisms have yet to be elucidated. Sirtuin 6 (Sirt6) has been implicated in obesity, insulin resistance, type 2 diabetes mellitus, and cardiovascular diseases. Sirt6 protects EC from premature senescence, oxidative stress, and atherosclerosis by sustaining high eNOS levels and preserving cell replication. How Sirt6 regulates coronary microvascular function remains to be determined. Methods: Inducible Sirt6 global knockout, endothelial-specific knockout, and wild-type (WT) mice were fed a diet high in fat and sugar (HFHS), and blood lipid and glucose were measured. Coronary arteries were isolated, and endothelial-dependent vasodilation (EDD) was assessed using myography (DMT). Echocardiography and treadmill exercise exertion tests were performed to evaluate cardiac function. Myocardial blood flow (MBF) was measured by doppler. Cardiac fibrosis was detected using trichrome staining, and molecular pathways were elucidated via gene and protein analysis. Results: Our preliminary data show that Sirt6 was downregulated in diabetes. The EDD of coronary arterioles Sirt6 global knockout and endothelial-specific knockout treated with HFHS was impaired, and the mediator of coronary vasodilation switched from NO to H 2 O 2 in the Sirt6 knockout mice. Compared to the WT mice, myocardial blood flow was decreased, ejection fraction (EF) was not changed, the running distance was reduced, and E/E’ ratio was increased in Sirt6 knockout mice. The Sirt6 targeted proteins were identified. Conclusions: Our suggest Sirt6 regulated coronary microvascular function through endothelial cells, and ablation of Sirt6 in endothelial cells caused CMD and diastolic dysfunction. Further genetic profiling will elucidate the pathways and mechanisms converging with Sirt6 to regulate microvascular function.
Abstract 15298: Paradoxical Association Between Sleep Duration and Risk of Stroke: Analysis of the National Health and Nutrition Examination Survey 2017 - 2020
Authors: Pakin Lalitnithi, Chawin Lopimpisuth, Chanattha Thimphitthaya, Watsachon Pangkanon, Phuuwadith Wattanachayakul, Chalothorn Wannaphut, Ekamol Tantisattamo
Journal: Circulation (2022)

Introduction: Although inadequate sleep is known to associate with cardiovascular (CV) outcomes including stroke, association between sleep duration and stroke is unclear. Hypothesis: Shorter sleep duration is associated with higher risk of stroke. Methods: A retrospective cross-sectional analysis of the 2017-2020 National Health and Nutrition Examination Survey (NHANES) included adult participants aged 21 to 79 years with self-reported history of stroke and sleep duration was studied. Association of sleep duration, stratified into short (&lt;6 hours) and normal sleep durations (≥6 hours), and stroke was evaluated by multivariate logistic regression. Results: A total of 8,416 participants were identified, of which mean age was 48.25±16 years old, 51.5% were female and mean sleep duration was 7.529 ± 1.651 hours. Overall, 377 patients (4.5%) had a stroke, of which mean sleep duration was 7.545 ± 2.132. Mean sleep duration of non-stroke population was 7.528 ± 1.626. The difference of mean sleep duration between these two groups was statistically significant (0.017 hours; P &lt; 0.001; 95% Cl -0.156,0.189; Figure1). The majority of the study participants reported a normal sleep duration (7426 participants, 88.2%) and the remaining 913 participants (10.8%) had a short sleep duration. Compared with the normal sleep duration group, participants with the short sleep duration had significantly lesser the odds of stroke (adjusted odds ratio 0.574; P &lt; 0.001; 95% CI 0.424,0.777) after adjusted for baseline risk factors including age, gender, ethnicity, body mass index (&lt;25 vs. ≥25 kg/m 2 ), history of hypertension and diabetes. Conclusions: Contrary to previous reports, this study shows that sleep duration is positively associated with risk of stroke. Further long-term studies that focus on understanding the pathophysiology using non-self-reported method are required to elucidate effect of sleep quality and optimal sleep duration on the adverse CV outcomes.
GOLD 2023 executive summary: comments from Asia's perspective
Authors: Fanny Wai San Ko, David Shu Cheong Hui
Journal: European Respiratory Journal (2023)

Asia has large country-to-country variations in COPD prevalence and mortality. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report covers many aspects of COPD, from causes and risk factors, to diagnosis, pharmacological and non-pharmacological treatment, and exacerbations [1]. We would like to make some comments on the relevance of the GOLD 2023 executive summary in Asia. GOLD 2023 executive summary: comments from Asia's perspective https://bit.ly/3zSvM9r
Abstract 271: The Time Dependence Of The Effect Of Extracorporeal Cpr For Out-of-hospital Cardiac Arrest Patients
Authors: Tasuku Matsuyama, Tetsuhisa Kitamura, Bon Ohta
Journal: Circulation (2022)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has been considered as a rescue therapy for refractory cardiac arrest patients. However, little is known about who is refractory to conventional CPR and when to judge the initiation of ECPR. Method: We performed a secondary analysis of the nationwide hospital-based prospective observational study (The JAAM-OHCA registry) in Japan. This study included adult OHCA patients aged ≥18 years who had an initial shockable rhythm between June, 2014 and December, 2019. We classified the included patients into the ECPR group or the conventional CPR group based on whether to receive ECPR or not. Low flow duration (LFD) was defined as the time from call to the initiation of ECPR or to the time of return of spontaneous circulation or termination of resuscitation. The primary outcome was 1-month survival with favorable neurological outcomes defined by cerebral performance category 1 or 2. We visually described the nonlinear relationship between LFD and the predictive probability of favorable neurological outcome using a restricted cubic spline by each group. Results: Of 57,754 patients registered in the JAAM-OHCA registry, 3807 patients were included in analyses (ECPR group, n = 865 and Conventional CPR group, n = 2942). In both groups, shorter LFD was associated with favorable neurological outcome. For first 30 minutes, the overall proportion of favorable neurological was higher in the Conventional CPR group, but due to the rapid decrease in Conventional CPR, it dropped down to almost the same probability before 20 min as that of shortest LFD around 25 min in the ECPR group. After that, the probability of favorable neurological outcome was constantly higher in the ECPR group. Conclusion: The judgement of refractory cardiac arrests and decision for ECPR should be delivered before 20 min from call to maximize the probability of favorable neurological outcome for those with an initial shockable rhythm.
Abstract 220: The Prediction Of Pulseless Electrical Activity Evolution During In-hospital Cardiac Arrest Using Machine Learning
Authors: Jon Urteaga, Elisabete Aramendi, Andoni Elola, Anders Norvik, Eirik Unneland, Abhishek Bhardwaj, David Buckler, Benjamin Abella, Eirik Skogvoll
Journal: Circulation (2022)

Background: Pulseless electrical activity (PEA) is the most common rhythm during in-hospital cardiac arrest (IHCA) with a prevalence around 50%. Knowing the prognosis of PEA evolution towards return of spontaneous circulation (ROSC) could help optimizing both resuscitation maneuvers and pharmacological therapy. The aim of this study was to develop an automatic method to predict the evolution of PEA during resuscitation based on the ECG-waveform. Materials and Methods: The dataset consists of 164 IHCA cases recorded by St. Olav University Hospital (Norway), Hospital of the University of Pennsylvania (USA) and Penn Presbyterian Medical Center (USA). ROSC was verified in 108 cases of the patients by physicians and bioengineers based on episode waveforms and clinical data. PEA segments of 5 sec were extracted from the last 10 min before ROSC or the end of resuscitation therapy. Three machine learning models were designed for segment binary classification based on an SVM (Gaussian) model using: 1) ECG-waveform features (9); 2) QRS-features (8); and 3) both ECG-waveform and QRS-features (17). Ten-fold cross validation was applied to train and test the models, and the performance was given in terms of area under the curve (AUC), sensitivity (Se) to correctly detect cases evolving to ROSC, specificity (Sp) and balanced accuracy (BAC). Results: A total of 780 segments were extracted (472 with ROSC). The median (IQR) for the models with the best feature combination are shown in the Table. The most important ECG-waveform features are associated to the ECG spectral distribution. QRS features that showed relevant information about the evolution of PEA were heart rate median and standard deviation, and QRS width, slope and amplitude. Conclusions: ROSC/no ROSC prediction of PEA segments is feasible using ECG signal information. The combination of ECG-waveform and QRS features enhances performance of predictive model.
Abstract 15415: Left Ventricular Unloading Reduces Right Ventricular Preload and Afterload in Patients With Acute Decompensated Heart Failure and Cardiogenic Shock
Authors: Kay D Everett, Pankaj Jain, Aaron Lee, Satoshi Miyashita, Michele Esposito, Richard Botto, Lara A Reyelt, Masashi Kawabori, Navin K Kapur
Journal: Circulation (2022)

Background: Use of the Impella 5.5 trans-valvular axial flow pump is increasing among patients with heart failure and cardiogenic shock (HF-CS) as a bridge to advanced therapies or myocardial recovery. The effect of trans-valvular left ventricular (LV) unloading on biventricular hemodynamics remains poorly understood. Methods: Seven patients with HF-CS underwent Impella 5.5 placement. A conductance catheter was placed first in the right ventricle (RV) then the LV to record pre-support pressure-volume loops. After insertion of the Impella 5.5, LV then RV loops were recorded within 15 minutes of device activation. Pulmonary artery catheter indices were recorded before and after Impella 5.5 activation. Results: Compared to baseline values, Impella 5.5 activation significantly decreased LV systolic and diastolic pressures as well as LV dP/dt(max) (Figure and Table). Impella 5.5 also significantly decreased right atrial, pulmonary (systolic/diastolic/mean) and RV diastolic pressures. Both LV and RV pressure-volume area and stroke work were not significantly changed with acute LV unloading. Conclusions: Trans-valvular unloading with an Impella 5.5 decreases biventricular filling pressures and reduces pulmonary pressures. These findings suggest that percutaneous LV unloading in patients with acute decompensated heart failure and cardiogenic shock may improve RV performance.
Abstract 204: Optic Nerve Sheath Diameter Trajectories During Targeted Temperature Management
Authors: Pavitra Kotini-Shah, Shaveta Khosla, Richard Gordon, Benjamin Karfunkle, Misha Granado, Jing Li, Terry L Vanden Hoek
Journal: Circulation (2022)

Introduction: The extent of hypoxic-ischemic injury (HII) after cardiac arrest (CA) remains an important knowledge deficit with lack of objective clinical data that is measurable repeatedly. There is a need to better understand an individual patient’s level of HII. Optic nerve sheath diameter (ONSD) has not been explored after CA as a possible bedside modality to measure the extent of HII over time, at the bedside, during targeted temperature management (TTM). Objective: We sought to characterize the temporal trajectories of point-of-care ultrasound obtained ONSD during the post- return of spontaneous circulation (ROSC) phase, in patients with and without TTM. Methods: Adult CA patients at an urban academic ED were included from 2017-2021. ONSD was measured by emergency ultrasound fellowship trained faculty at 1, 6, 24, 48, and 72 hours after ROSC using an ocular preset on a 15MHz linear probe. ONSD measurements at these time points were compared with patient demographic information and intervention of TTM . Results: A total of 78 participants had ONSD measurements. The mean age was 62 (+/-15) and 46% were female. Of the 65% of the cases with TTM, a sex disparity was noted with 73% of males receiving TTM versus 56% of females. There was a trend toward a decrease in mean ONSD by 0.015cm for TTM patients during the early time points of 1 to 6 hours compared to an increase in 0.006cm in those without TTM. Similar trend was noted between 1 to 24 hours, with a decrease in ONSD by 0.025cm in those with TTM relative to an average increase of 0.008 cm in those without TTM. However, neither delta ONSD was statistically significant between the two cohorts. When further assessing if delay in cooling had an impact on ONSD change, we found that the ONSD change between 24 to 48 hours was significantly increased in those in whom TTM was not initiated within 14 hours (beta=0.036; p=0.016). Conclusion: This pilot study revealed ONSD changes during TTM. There is potential for monitoring brain injury through ONSD trajectories to evaluate responders vs non-responders to TTM. Additional research is needed to evaluate ONSD changes during the rewarming time frame and may further distinguish patients with worse HII. Correlation to survival outcomes can be possible with a larger sample size.
Abstract 15337: Chronic Oral Finerenone Treatment Does Not Improve Left Ventricular Diastolic Compliance in Swine With Repetitive Pressure Overload-Induced HFpEF
Authors: Emily Hudson, Samantha Spinella, Dorcas Nsumbu, Beth Palka, John M Canty, Brian R Weil
Journal: Circulation (2022)

Introduction: The non-steroidal mineralocorticoid receptor antagonist finerenone has emerged as a potential treatment for heart failure with preserved ejection fraction (HFpEF) based, in part, on initial evidence of its anti-fibrotic properties. However, it is unclear whether chronic oral finerenone therapy can reverse established cardiac fibrosis. Accordingly, we tested the efficacy of chronic oral finerenone in a porcine model of HFpEF characterized by interstitial fibrosis and reduced left ventricular (LV) diastolic compliance in the absence of co-morbidities or anatomic LV hypertrophy. Methods: Swine (n=12) were subjected to daily (1 hr) episodes of repetitive LV pressure overload (RPO) for 2 weeks using phenylephrine (24 mg/hr) to transiently elevate LVEDP to ~30 mm Hg. After 2 weeks, RPO was discontinued and animals were followed for an additional 4 weeks, during which a subset received oral finerenone (20 mg/day; n=6). LV end-diastolic volume (EDV) and pressure (EDP) were measured at normal and elevated preload to assess LV compliance (ΔLVEDV/ΔLVEDP) and post-mortem picrosirius red staining was performed to quantify interstitial fibrosis vs. normal controls (n=8). Results: Four-weeks after cessation of RPO, untreated animals exhibited a significant increase in interstitial fibrosis vs. normal controls that was attenuated in finerenone-treated animals ( Figure A ). Despite this regression of interstitial collagen, a persistent reduction in LV diastolic compliance was observed after finerenone treatment (1.18 ± 0.33 mL/mmHg vs. 2.11 ± 0.22 mL/mmHg in normal controls; p=0.04) that was comparable to that of untreated animals after RPO (0.97 ± 0.22 mL/mmHg; p=0.61; Figure B ). Conclusion: Four weeks of chronic oral finerenone treatment does not restore LV diastolic compliance in swine with RPO-induced HFpEF despite regression of interstitial collagen content, suggesting that other factors may contribute to diastolic stiffening in this model.
Abstract 15868: Prevalence and Effects of Acute Myocardial Infarction on Hospital Outcomes Among COVID-19 Patients
Authors: Sandeep Appunni, Venkataraghavan Ramamoorthy, Zhenwei Zhang, Md Ashfaq Ahmed, Peter McGranaghan, Joseph Salami, Ramez Morcos, Muni Rubens, Anshul Saxena, Emir Veledar, Javier Jimenez, Sandra Chaparro
Journal: Circulation (2022)

Introduction: In the US, there are approximately 84 million cases of COVID-19 accounting for 1 million deaths. Though there are not many studies, acute myocardial infarction (AMI) is one of the most lethal complications of COVID-19. In this study, we looked for occurrence of AMI and its effects on hospital outcomes among COVID-19 patients. Hypothesis: AMI among COVID-19 hospitalizations could worsen the levels of adverse in-hospital outcomes. Methods: Data from the 2020 California State Inpatient Database was used retrospectively. All COVID-19 hospitalizations with age ≥18 years were included in the analyses. Adverse hospital outcomes included in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and ICU admission. Prolonged length of stay included any hospital length of stay ≥75th percentile. We explored for differences in adverse hospital outcomes between those with and without AMI. Multivariate logistic regression analyses were used to understand the strength of these associations after adjusting for cofactors. Results: Our analysis had a total of 94,114 COVID-19 hospitalizations and 1548 (1.6%) had AMI. Adverse hospital outcomes such as mortality (43.2% versus 10.8%, P&lt;0.001), prolonged length of stay (39.9% versus 28.2%, P&lt;0.001), vasopressor use (7.8% versus 2.1%, P&lt;0.001), mechanical ventilation (35.0% versus 9.7%, P&lt;0.001), and ICU admission (33.0% versus 9.4%, P&lt;0.001) were significantly higher among COVID-19 hospitalizations with AMI. The odds of adverse outcomes such as mortality (aOR, 3.90, 95% CI: 3.48-4.36), prolonged length of stay (aOR, 1.23, 95% CI: 1.10-1.37), vasopressor use (aOR, 3.71, 95% CI: 3.30-4.17), mechanical ventilation (aOR, 2.71, 95% CI: 2.21-3.32), and ICU admission (aOR, 3.51, 95% CI: 3.12-3.96) were significantly more prevalent among COVID-19 hospitalizations with AMI. Conclusions: In spite of very low prevalence of AMI among COVID-19 hospitalizations, we observed a substantially greater risk of adverse hospital outcomes and mortality. The hyperinflammatory response of COVID-19 could additionally worsen the factors precipitating mortality among AMI. COVID-19 patients with AMI should be aggressively treated to improve hospital outcomes.
Abstract 216: Association Between Trajectories Of End-tidal Carbon Dioxide And Return Of Spontaneous Circulation Among Emergency Department Patients With Out-of-hospital Cardiac Arrest: A Retrospective Analysis Of A Prospective Registry
Authors: CHIH-HUNG WANG, Tsung-Chien Lu, Chong Kah Meng, Eric H Chou, Chu-Lin Tsai, CHIEN-HUA HUANG, Matthew H Huei-Ming, Wen-Jone Chen
Journal: Circulation (2022)

Introduction: The level of end-tidal carbon dioxide (EtCO 2 ) reflects the blood flow generated by cardiopulmonary resuscitation (CPR). Static EtCO 2 parameters, such as average EtCO 2 levels, has been reported to be associated with outcomes following out-of-hospital cardiac arrest (OHCA). Hypothesis: Distinct trajectories of EtCO 2 during CPR was associated with OHCA outcomes. Methods: This was a retrospective analysis of a prospectively collected database on patients with OHCA who had been resuscitated in the emergency department of a tertiary medical center between 2015 and 2020. Adult patients with ≥3 measurements of EtCO 2 were included. The primary outcome was the return of spontaneous circulation (ROSC). Group-based trajectory modelling was used to identify the EtCO 2 trajectories. Multivariable logistic regression analysis was performed to evaluate the association between EtCO 2 trajectories and ROSC. The predictive performance of the EtCO 2 trajectories was assessed using the area under the receiver operating characteristic curve (AUC). Results: The study comprised 655 patients with OHCA. In the primary analysis, three distinct EtCO 2 trajectories, including 10-mmHg, 30-mmHg, and 50-mmHg trajectories, were identified. Compared with the 10-mmHg trajectory, both 30-mmHg (odds ratio [OR]: 4.66, 95% confidence interval [CI]: 3.15-6.90) and 50-mmHg (OR: 7.58, 95% CI: 4.30-13.35) trajectories were associated with a higher likelihood of ROSC. In a sensitivity analysis of excluding EtCO 2 measured before tracheal intubation or after sodium bicarbonate administration, the predictive ability of the identified EtCO 2 trajectories remained. As a single predictor of ROSC, EtCO 2 trajectories had an acceptable discriminative performance (AUC: 0.69, 95% CI: 0.66-0.73). Conclusion: Three distinct EtCO 2 trajectories during CPR were identified and significantly associated with OHCA outcomes, which may assist in guiding the ongoing resuscitation efforts.